a study to evaluate the efficacy and safety of gantenerumab in participants at risk for or at the earliest stages of alzheimer's disease (ad)

Conditions: Alzheimers Disease

Summary: a study to evaluate the efficacy and safety of gantenerumab in amyloid-positive, cognitively unimpaired participants at risk for or at the earliest stages of ad. the planned number of participants for this study is approximately 1200 participants randomized in a 1:1 ratio to receive either gantenerumab or placebo (600 participants randomized to gantenerumab and 600 participants randomized to placebo).


Eligibility criteria:
key inclusion criteria: * willing and able to comply with the study protocol and complete all aspects of the study \[including cognitive and functional assessments, physical and neurological examinations, mri, csf collection, genotyping, and positron emission tomography (pet) imaging\]. * cognitively unimpaired with a screening clinical dementia rating global score (cdr-gs) of 0, and repeatable battery for the assessment of neuropsychological status delayed memory index (rbans dmi) \>=80. * evidence of cerebral amyloid accumulation. * participants who have an available person (referred to as a "study partner"). * fluent in the language of the tests used at the study site. * adequate visual and auditory acuity, sufficient to perform neuropsychological testing (eye glasses and hearing aids are permitted). * agreed not to participate in other interventional research studies for the duration of this trial. * for women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 17 weeks after the final dose of study treatment. key exclusion criteria: * any evidence of an underlying neurological or neurodegenerative condition that may lead to cognitive impairment other than ad. * clinical diagnosis of mild cognitive impairment (mci), prodromal ad, or any form of dementia. * history or presence of intracranial or intracerebral vascular malformations, aneurysm, subarachnoid hemorrhage, or intracerebral macrohemorrhage. * history or presence of posterior reversible encephalopathy syndrome. * history of ischemic stroke with clinical symptoms or an acute event that is consistent with a transient ischemic attack within 12 months of screening. * history of severe, clinically significant (i.e., resulting in persistent neurologic deficit or structural brain damage) central nervous system (cns) trauma (e.g., cerebral contusion). * history or presence of intracranial mass lesion (e.g., glioma, meningioma) that could potentially impair cognition or lead to progressive neurological deficits. * infections that may affect brain function or a history of infections that resulted in neurologic sequelae \[e.g., human immunodeficiency virus (hiv), syphilis, neuroborreliosis, and viral or bacterial meningitis and encephalitis\]. * history of major depression, schizophrenia, schizoaffective disorder, or bipolar disorder. * at risk for suicide. * history of alcohol and/or substance abuse or dependence. * history or presence of clinically significant systemic vascular disease, atrial fibrillation or heart failure. * within the last year, experienced unstable or clinically significant cardiovascular disease (e.g., myocardial infarction). * uncontrolled hypertension. * chronic kidney disease, indicated by creatinine clearance \<30 ml/min. * confirmed and unexplained impaired hepatic function. * history of, or are known to currently have an hiv infection, or hepatitis b or hepatitis c virus infection that has not been adequately treated. * history or presence of systemic autoimmune disorders that may lead to progressive neurological impairment with associated cognitive deficits. * systemic immunosuppression or immunomodulation due to the continuing effects of immunosuppressant or immunomodulating medications. * current covid-19 infection. * evidence of folic acid or vitamin b-12 deficiency. * any passive immunotherapy (ig) or other long-acting biologic agent to prevent or postpone cognitive decline within 1 year of screening. * any other investigational treatment within 5 half-lives or 6 months (whichever is longer) prior to screening. * typical/atypical anti-psychotic medications or neuroleptic medications. * anticoagulation medications within 3 months of screening with no plans to initiate any prior to randomization. * any previous treatment with cholinesterase inhibitors and n-methyl-d-aspartate receptor antagonists are exclusionary at screening. * pregnant or breastfeeding, or intending to become pregnant during the study or within 17 weeks after the final dose of gantenerumab. * impaired coagulation. * known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins, including gantenerumab and gantenerumab excipients. * participants who reside in a skilled nursing facility such as a convalescent home or long-term care facility. * participants who require residence in such facilities during the study may continue in the study and be followed for efficacy and safety, provided that they have a study partner who meets the study partner requirements.